As people have longer lifespan with changes in diet habits, cancer patients have increased from year to year. WHO data shows that cancer has become a major fatal disease, and cancer patients will continue to increase; cancer as the leading cause of death in 2008 accounted for 13.8%, and is expected to account for more than 15% in 2015.
Currently, the clinical treatments of malignant tumors are primarily by surgery, radiotherapy, and chemotherapy, either alone or in combination. In recent years, the survival time of cancer patients was significantly prolonged by chemotherapy. However, existing anticancer drugs still cannot meet the clinical needs due to the high variability of tumor cells and the generation of multi-drug resistance. Cytotoxic drugs as a major component of chemotherapy in cancer treatment have played a very important role. So far, these drugs still occupy major market share of anticancer drugs, including drugs obtained from natural products, such as Taxol drugs, etc., and they become common anti-cancer drugs in clinical practices because of their therapeutic effects.
Nevertheless, cytotoxic chemotherapy drugs can cause multi-drug resistance of the tumor cells after long-term using, which reduce the efficacy of these drugs, such that doctors increase drug dosage to improve efficacy, thereby reducing drug security. Adverse reactions would be caused because cytotoxic drugs kill tumor cells while also killing normal cells. All cytotoxic drugs usually lead to adverse reactions in patients, and the adverse reactions are increasing in accordance with the increasing dosage. Therefore, the maximum dose of chemotherapeutic drug is strictly limited. In other words, it is not feasible to increase administration to improve drug efficacy when the drug resistance occur. The only feasible way is to replace another effective chemotherapy drug. Thus, more effective chemotherapy drugs shall be developed for clinicians, and the research and development of new and effective anticancer drugs is undoubtedly one of the most urgent tasks.
Garcinia (Gamboge) is yellow resin from gamboge trees that grow in India, Vietnam, and in Yunnan, Hunan, and Hubei areas in China, and can be used as a yellow pigment in painting. The book “Compendium of Materia Medica” authored by Li Shizhen of the Ming Dynasty cited that “Garcinia used for painter was decocted”. Garcinia is one of the Chinese medicines that inhibit tumor growth and refractory carbuncle.
Gambogenic acid (as shown in Formula X, numbers representing a carbon sequence) is the active ingredient of Garcinia. It has been reported that gambogenic acid can inhibit tumor growth in vitro and in vivo, induce tumor cells apoptosis, and show stronger anti-tumor activities for a variety of malignant tumors due to it's characteristic of selectively inhibiting tumor growth.

Bao-Xi, Qu etc. (Chinese Journal of Clinical Oncology, 1991, Volume 18, No. 1, page 50) demonstrated that gambogenic acid has broad anti-cancer activities, less toxicity, and better inhibitory effect for inhibiting S180, ARS ascites carcinoma, P388 leukemia, Lewis lung cancer and La795 lung cancer. In comparison with garcinia acid (another anti-tumor components extracted from Garcinia), gambogenic acid is stronger for inhibiting mouse leukemia L1210, and the highest survival rate of gambogenic acid is extended up to 2.45 times than that of garcinia acid. The research results of cell cycle of L1210 leukemia show that gambogenic acid (intravenous infusion, 10 mg/kg) can inhibit G1-S phase transition by reducing S phase cells and promoting G1 phase cells.
Cheng Hui, etc. (Herbal, 2008, Volume 39 No. 2, page 236) observed proliferative inhibition of a variety of malignant cells by gambogenic acid via MTT method. The result showed that gambogenic acid can be significantly used for proliferative inhibition of human colon cancer cells (HCT-8), human hepatoma cells (BEL-7402), human gastric cancer cells (BGC-823), human non-small cell lung cancer cells (A549), and human ovarian cancer (A2780).
Gambogenic acid is a common active ingredient in traditional Chinese medicine. The extraction process of gambogenic acid is simple, low cost, and gambogenic acid can be obtained plentifully for developing anti-tumor drug.
Patent CN1718183A disclosed gambogenic acid preparation can inhibit human hepatoma BEL-7402, human hepatoma 7721, human breast cancer MCF-7, and human cervical carcinoma Hela cells, wherein the human hepatoma cells are most sensitive. Patent CN1718184A disclosed gambogenic acid complexes combined with anticancer drugs such as moroxydine, amantadine, cytarabine, and matrine for the treatment of liver cancer, colon cancer, and lung cancer due to prominent efficacy and lower irritation and toxicity. Patent CN101947204A disclosed solid lipid nanoparticles of gambogenic acid: preparing gambogenic acid to make solid nanoparticles to improve bioavailability, reduce irritation, and prolong efficacy time.
In comparison with the current clinical drugs, gambogenic acid obtained from nature has shortcomings including that the activity is not strong enough, and safe dose is small, thereby limiting its development and application. Thus, the structure of the gambogenic acid has to be modified to improve its activity and druggability.